tbuckley/cabot-search huggingface dataset:
EPI-Net One Health reporting guideline for antimicrobial consumption and resistance surveillance data: a Delphi approach
Authors: Nithya Babu Rajendran, Fabiana Arieti, Carla Alejandra Mena-Benítez, Liliana Galia, Maela Tebon, Julio Alvarez, Beryl Primrose Gladstone, Lucie Collineau, Giulia De Angelis, Raquel Duro, William Gaze, Siri Göpel, Souha S. Kanj, Annemarie Käsbohrer, Direk Limmathurotsakul, Estibaliz Lopez de Abechuco, Elena Mazzolini, Nico T. Mutters, Maria Diletta Pezzani, Elisabeth Presterl, Hanna Renk, Jesús Rodríguez-Baño, Oana Săndulescu, Federico Scali, Robert Skov, Thirumalaisamy P. Velavan, Cuong Vuong, Evelina Tacconelli, Ayola Akim Adegnika, Lisa Avery, Marc Bonten, Alessandro Cassini, Claire Chauvin, Monica Compri, Peter Damborg, Sabine De Greeff, Maria Dolores Del Toro, Matthias Filter, Alison Franklin, Bruno Gonzalez-Zorn, Kari Grave, Didier Hocquet, Ludwig E. Hoelzle, Erta Kalanxhi, Ramanan Laxminarayan, Leonard Leibovici, Surbhi Malhotra-Kumar, Marc Mendelson, Mical Paul, Cristina Muñoz Madero, Rita Murri, Laura J.V. Piddock, Carolien Ruesen, Maurizio Sanguinetti, Thorben Schilling, Remco Schrijver, Mitchell J. Schwaber, Luigia Scudeller, Didem Torumkuney, Thomas Van Boeckel, Wannes Vanderhaeghen, Andreas Voss, Teresa Wozniak
Journal: The Lancet Regional Health - Europe (2022)

Strategic and standardised approaches to analysis and reporting of surveillance data are essential to inform antimicrobial resistance (AMR) mitigation measures, including antibiotic policies. Targeted guidance on linking full-scale AMR and antimicrobial consumption (AMC)/antimicrobial residues (AR) surveillance data from the human, animal, and environmental sectors is currently needed. This paper describes the initiative whereby a multidisciplinary panel of experts (56 from 20 countries-52 high income, 4 upper middle or lower income), representing all three sectors, elaborated proposals for structuring and reporting full-scale AMR and AMC/AR surveillance data across the three sectors. An evidence-supported, modified Delphi approach was adopted to reach consensus among the experts for dissemination frequency, language, and overall structure of reporting; core elements and metrics for AMC/AR data; core elements and metrics for AMR data. The recommendations can support multisectoral national and regional plans on antimicrobials policy to reduce resistance rates applying a One Health approach.
ESCMID/EUCIC clinical practice guidelines on perioperative antibiotic prophylaxis in patients colonized by multidrug-resistant Gram-negative bacteria before surgery
Authors: Elda Righi, Nico T. Mutters, Xavier Guirao, Maria Dolores del Toro, Christian Eckmann, Alex W. Friedrich, Maddalena Giannella, Jan Kluytmans, Elisabeth Presterl, Eirini Christaki, Elizabeth L.A. Cross, Alessandro Visentin, Gabriele Sganga, Constantinos Tsioutis, Evelina Tacconelli
Journal: Clinical Microbiology and Infection (2022)
Modulation of RNA splicing enhances response to BCL2 inhibition in leukemia
Authors: Eric Wang, Jose Mario Bello Pineda, Won Jun Kim, Sisi Chen, Jessie Bourcier, Maximilian Stahl, Simon J. Hogg, Jan Phillipp Bewersdorf, Cuijuan Han, Michael E. Singer, Daniel Cui, Caroline E. Erickson, Steven M. Tittley, Alexander V. Penson, Katherine Knorr, Robert F. Stanley, Jahan Rahman, Gnana Krishnamoorthy, James A. Fagin, Emily Creger, Elizabeth McMillan, Chi-Ching Mak, Matthew Jarvis, Carine Bossard, Darrin M. Beaupre, Robert K. Bradley, Omar Abdel-Wahab
Journal: Cancer Cell (2022)

Therapy resistance is a major challenge in the treatment of cancer. Here, we performed CRISPR-Cas9 screens across a broad range of therapies used in acute myeloid leukemia to identify genomic determinants of drug response. Our screens uncover a selective dependency on RNA splicing factors whose loss preferentially enhances response to the BCL2 inhibitor venetoclax. Loss of the splicing factor RBM10 augments response to venetoclax in leukemia yet is completely dispensable for normal hematopoiesis. Combined RBM10 and BCL2 inhibition leads to mis-splicing and inactivation of the inhibitor of apoptosis XIAP and downregulation of BCL2A1, an anti-apoptotic protein implicated in venetoclax resistance. Inhibition of splicing kinase families CLKs (CDC-like kinases) and DYRKs (dual-specificity tyrosine-regulated kinases) leads to aberrant splicing of key splicing and apoptotic factors that synergize with venetoclax, and overcomes resistance to BCL2 inhibition. Our findings underscore the importance of splicing in modulating response to therapies and provide a strategy to improve venetoclax-based treatments.
Author correction to ‘Ablation of Akt2 and AMPKα2 rescues high fat diet-induced obesity and hepatic steatosis through Parkin-mediated mitophagy’ [Acta Pharmaceutica Sinica B 11 (2021) 3508–3526]
Authors: Shuyi Wang, Jun Tao, Huaguo Chen, Machender R. Kandadi, Mingming Sun, Haixia Xu, Gary D. Lopaschuk, Yan Lu, Junmeng Zheng, Hu Peng, Jun Ren
Journal: Acta Pharmaceutica Sinica B (2022)

[This corrects the article DOI: 10.1016/j.apsb.2021.07.006.].
Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment
Authors: Lin Hou, Xueyuan Peng, Ruiting Wang, Yifei Wang, Hong Li, Huijuan Zhang, Yun Zhang, Zhenzhong Zhang
Journal: Acta Pharmaceutica Sinica B (2022)

Type 2 diabetes mellitus (T2DM) therapy is facing the challenges of long-term medication and gradual destruction of pancreatic islet β-cells. Therefore, it is timely to develop oral prolonged action formulations to improve compliance, while restoring β-cells survival and function. Herein, we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property, which combined apical sodium-dependent bile acid transporter-mediated intestinal uptake and lymphatic transportation. In this system, taurocholic acid (TCA) modified poly(lactic-co-glycolic acid) (PLGA) was employed to achieve pancreas location, hydroxychloroquine (HCQ) was loaded to execute therapeutic efficacy, and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) was introduced as stabilizer together with synergist (PLGA-TCA/DLPC/HCQ). In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction, thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day. In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress, remodeled the inflammatory pancreas microenvironment, and activated PI3K/AKT signaling pathway without obvious toxicity. This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.
Intelligent nanotherapeutic strategies for the delivery of CRISPR system
Authors: Chao Chen, Wu Zhong, Shiyu Du, Yayao Li, Yunfei Zeng, Kunguo Liu, Jingjing Yang, Xiaoxiang Guan, Xin Han
Journal: Acta Pharmaceutica Sinica B (2022)

CRISPR, as an emerging gene editing technology, has been widely used in multiple fields due to its convenient operation, less cost, high efficiency and precision. This robust and effective device has revolutionized the development of biomedical research at an unexpected speed in recent years. The development of intelligent and precise CRISPR delivery strategies in a controllable and safe manner is the prerequisite for translational clinical medicine in gene therapy field. In this review, the therapeutic application of CRISPR delivery and the translational potential of gene editing was firstly discussed. Critical obstacles for the delivery of CRISPR system in vivo and shortcomings of CRISPR system itself were also analyzed. Given that intelligent nanoparticles have demonstrated great potential on the delivery of CRISPR system, here we mainly focused on stimuli-responsive nanocarriers. We also summarized various strategies for CIRSPR-Cas9 system delivered by intelligent nanocarriers which would respond to different endogenous and exogenous signal stimulus. Moreover, new genome editors mediated by nanotherapeutic vectors for gene therapy were also discussed. Finally, we discussed future prospects of genome editing for existing nanocarriers in clinical settings.
Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndrome
Authors: Martin C J Kneyber, Robinder G Khemani, Anoopindar Bhalla, Robert G T Blokpoel, Pablo Cruces, Mary K Dahmer, Guillaume Emeriaud, Jocelyn Grunwell, Stavroula Ilia, Bhushan H Katira, Yolanda M Lopez-Fernandez, Prakadeshwari Rajapreyar, L Nelson Sanchez-Pinto, Peter C Rimensberger
Journal: The Lancet Respiratory Medicine (2022)
Neurodevelopmental Disorders in Offspring Conceived via In Vitro Fertilization vs Intracytoplasmic Sperm Injection
Authors: Huiwen Lo, Shih-Feng Weng, Eing-Mei Tsai
Journal: JAMA Network Open (2022)

Importance Intracytoplasmic sperm injection (ICSI), the most common type of assisted reproductive technology (ART), might damage the sperm or embryo. The implications of male infertility and ICSI for the neurodevelopmental health of offspring remain unknown. Objective To analyze the risks of neurodevelopmental disorders in offspring of couples with male or female infertility with or without ICSI use. Design, Setting, and Participants This cohort study was conducted in Taiwan and used information collected from the national population registry data set, national birth data set, and national ART data set for all live singleton births from January 1, 2008, to December 31, 2016. The follow-up period started from the date of birth until the diagnosis of a disorder or December 31, 2018, whichever occurred first. Data were analyzed from July 1, 2021, to August 1, 2022. Exposures Male or female infertility with or without ICSI. Main Outcomes and Measures The outcome was the incidence of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and developmental delay in offspring with ART conception. Taiwan’s national population registry data set was used to identify ASD, ADHD, and developmental delay diagnosed in outpatient clinic and hospitalization records. Results The study included 1 575 971 singleton births (mean [SD] age, 5.87 [2.60] years; 819 389 boys [52.0%]), of whom 1 568 257 (99.5%) had natural conception, 2111 (0.1%) had ART conception with male infertility, and 5603 (0.4%) had ART conception with female infertility. The risks of ASD (adjusted hazard ratio, 2.49; 95% CI, 1.61-3.84; P &amp;amp;lt; .001) and developmental delay (adjusted hazard ratio, 1.92; 95% CI, 1.54-2.39; P &amp;amp;lt; .001) in offspring with ART conception and ICSI use were significantly higher than those in offspring with natural conception. The same results were found in offspring of couples with either male or female infertility and ICSI intervention. Conclusions and Relevance Results of this study suggest that male infertility was not associated with an increased risk of neurodevelopmental disorders in offspring. In both male and female infertility groups, ICSI had unfavorable implications for the neurodevelopmental health of offspring in terms of increased risks of ASD and developmental delay.
Survival After Minimally Invasive vs Open Surgery for Pancreatic Adenocarcinoma
Authors: Halit Topal, Raymond Aerts, Annouschka Laenen, André Collignon, Joris Jaekers, Joachim Geers, Baki Topal
Journal: JAMA Network Open (2022)

Importance Only a few high-volume centers have reported on long-term oncologic outcomes after minimally invasive pancreatic surgery (MIPS) for pancreatic adenocarcinoma, but none of them have shown superior long-term overall survival (OS) compared with open pancreatic surgery (OPS). Objective To study long-term survival after MIPS and OPS with curative intent among patients with pancreatic adenocarcinoma. Design, Setting, and Participants This comparative effectiveness study used a retrospective analysis of a prospectively maintained electronic database of patient data collected between January 2010 and December 2019. Consecutive patients from a high-volume pancreatic cancer referral center were included. Data analysis was conducted from March to October 2022. Median follow-up time was 56.8 months. Exposures Patients were matched using propensity score models to study long-term survival. Main Outcomes and Measures Survival outcomes were analyzed using the Cox proportional hazards model. Variables used for propensity score correction were TNM stage, tumor dimension, lymph node status, type of operation, simultaneous vascular resection, neoadjuvant chemotherapy, adjuvant chemotherapy, sex, age, and American Society of Anesthesiologists score. Additional corrections were made for year of surgery and type of adjuvant chemotherapy. Results After propensity score matching the sample of 396 patients, there were 198 patients in the MIPS group (89 [44.9%] men; median [range] age, 68 [32-87] years) and 198 in the OPS group (94 [47.5%] men; median [range] age, 67 [39-84] years). Median OS in the MIPS group was 30.7 (95% CI, 26.2-36.8) months compared with 20.3 (95% CI, 17.6-23.5) months after OPS (hazard ratio [HR], 0.70; 95% CI, 0.56-0.87; P = .002). Median disease-free survival (DFS) after MIPS vs OPS was 14.8 (95% CI, 11.8-17.0) months vs 10.7 (95% CI, 9.0-12.1) months (HR, 0.71; 95% CI, 0.57-0.89; P = .003). Additional corrections for year of surgery and type of adjuvant chemotherapy showed better OS (year of surgery: HR, 0.74; 95% CI, 0.57-0.96; P = .02; adjuvant chemotherapy: HR, 0.71; 95% CI, 0.56-0.90; P = .005) and DFS (year of surgery: HR, 0.77; 95% CI, 0.59-0.99; P = .04; adjuvant chemotherapy: HR, 0.72; 95% CI, 0.57-0.92; P = .009) for patients undergoing minimally invasive vs open surgery. Conclusions and Relevance In this study of 396 patients with borderline resectable and resectable pancreatic adenocarcinoma, MIPS was associated with better OS and DFS than OPS. Centralization of MIPS should be stimulated, and pancreatic surgeons should be encouraged to pass the learning curve before implementing MIPS for pancreatic adenocarcinoma in daily clinical practice.
Assessing Performance and Clinical Usefulness in Prediction Models With Survival Outcomes: Practical Guidance for Cox Proportional Hazards Models
Authors: David J. McLernon, Daniele Giardiello, Ben Van Calster, Laure Wynants, Nan van Geloven, Maarten van Smeden, Terry Therneau, Ewout W. Steyerberg, David J. McLernon, Daniele Giardiello, Ben Van Calster, Laure Wynants, Nan van Geloven, Maarten van Smeden, Terry Therneau, Ewout W. Steyerberg, Patrick Bossuyt, Tom Boyles, Gary Collins, Kathleen Karr, Petra Macaskill, Carl Moons, Andrew Vickers, Max Westphal, Michal Abrahamowicz, Malka Gorfine, Federico Ambrogi, Richard Cook, Pierre Joly, Per Kragh Andersen, Torben Martinussen, Maja Pohar-Perme, Hein Putter, Jeremy Taylor
Journal: Annals of Internal Medicine (2022)

Risk prediction models need thorough validation to assess their performance. Validation of models for survival outcomes poses challenges due to the censoring of observations and the varying time horizon at which predictions can be made. This article describes measures to evaluate predictions and the potential improvement in decision making from survival models based on Cox proportional hazards regression. As a motivating case study, the authors consider the prediction of the composite outcome of recurrence or death (the "event") in patients with breast cancer after surgery. They developed a simple Cox regression model with 3 predictors, as in the Nottingham Prognostic Index, in 2982 women (1275 events over 5 years of follow-up) and externally validated this model in 686 women (285 events over 5 years). Improvement in performance was assessed after the addition of progesterone receptor as a prognostic biomarker. The model predictions can be evaluated across the full range of observed follow-up times or for the event occurring by the end of a fixed time horizon of interest. The authors first discuss recommended statistical measures that evaluate model performance in terms of discrimination, calibration, or overall performance. Further, they evaluate the potential clinical utility of the model to support clinical decision making according to a net benefit measure. They provide SAS and R code to illustrate internal and external validation. The authors recommend the proposed set of performance measures for transparent reporting of the validity of predictions from survival models.
Profiling of Tumor Cell‐Delivered Exosome by Surface Enhanced Raman Spectroscopy‐Based Biosensor for Evaluation of Nasopharyngeal Cancer Radioresistance
Authors: Qiong Wu, Qin Ding, Wanzun Lin, Youliang Weng, Shangyuan Feng, Rong Chen, Chuanben Chen, Sufang Qiu, Duo Lin
Journal: Advanced Healthcare Materials (2022)

Although the advancement of radiotherapy significantly improves the survival of nasopharyngeal cancer (NPC), radioresistance associated with recurrence and poor outcomes still remains a daunting challenge in the clinical scenario. Currently, effective biomarkers and convenient detection methods for predicting radioresistance have not been well established. Here, the surface-enhanced Raman spectroscopy combined with proteomics is used to firstly profile the characteristic spectral patterns of exosomes secreted from self-established NPC radioresistance cells, and reveals specific variations of proteins expression during radioresistance formation, including collagen alpha-2 (I) chain (COL1A2) that is associated with a favorable prognosis in NPC and is negatively associated with DNA repair scores and DNA repair-related genes via bioinformatic analysis. Furthermore, deep learning model-based diagnostic model is generated to accurately identify the exosomes from radioresistance group. This work demonstrates the promising potential of exosomes as a novel biomarker for predicting the radioresistance and develops a rapid and sensitive liquid biopsy method that will provide a personalized and precise strategy for clinical NPC treatment.
Oxidative Stress Amplifiers as Immunogenic Cell Death Nanoinducers Disrupting Mitochondrial Redox Homeostasis for Cancer Immunotherapy
Authors: Jia Wan, Xianghong Zhang, Zhihong Li, Fuhao Mo, Dongsheng Tang, Haihua Xiao, Jingcheng Wang, Guanghua Rong, Tang Liu
Journal: Advanced Healthcare Materials (2022)

Abstract Reactive oxygen species (ROS)‐induced oxidative stress in the endoplasmic reticulum (ER) is generally believed to be an important prerequisite for immunogenic cell death (ICD) which can trigger antitumor immune responses for cancer immunotherapy. However, thus far, little is known between the oxidative stress in a certain organelle other than ER and ICD. Herein, polymers for preparing ROS‐responsive nanoparticles (NP‐I‐CA‐TPP) with mitochondrial targeting performance as ICD nanoinducers are designed. It is believed that NP‐I‐CA‐TPP can target mitochondria which are extremely important organelles intimately involved in cellular stress signaling to play an important role in the induction of ICD. NP‐I‐CA‐TPP can amplify cinnamaldehyde (CA)‐induced ROS damage by iodo–thiol click chemistry‐mediated glutathione depletion in cancer cells. Finally, NP‐I‐CA‐TPP is shown to disrupt mitochondrial redox homeostasis, amplify mitochondrial oxidative stress, promote cancer cell apoptosis via inducing ICD, and triggering the body's antitumor immune response for cancer immunotherapy.
Association of longer telomere length in cancer cells and cancer-associated fibroblasts with worse prognosis
Authors: Yoko Matsuda, Juanjuan Ye, Keiko Yamakawa, Yuri Mukai, Kazuki Azuma, Linxuan Wu, Kenkichi Masutomi, Taro Yamashita, Yataro Daigo, Yohei Miyagi, Tomoyuki Yokose, Takashi Oshima, Hiroyuki Ito, Soichiro Morinaga, Takeshi Kishida, Toshinari Minamoto, Motohiro Kojima, Shuichi Kaneko, Reiji Haba, Keiichi Kontani, Nobuhiro Kanaji, Keiichi Okano, Mariko Muto-Ishizuka, Masanao Yokohira, Kousuke Saoo, Katsumi Imaida, Futoshi Suizu
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background Telomere dysfunction has been reported to be directly involved in carcinogenesis owing to chromosomal instability and immortalization; however, the clinicopathological significance of telomeres remains controversial. We have shown that telomere shortening occurs in normal-appearing duct cells at initiation and then continues during the progression of pancreatic cancer. In this study, we determined the clinicopathological and prognostic value of telomere length (TL) in cancer progression. Methods TL in both cancer cells and cancer-associated fibroblasts (CAFs) was analyzed by high-throughput quantitative fluorescence in situ hybridization using a previously reported cohort comprising 1434 cases of adenocarcinoma (ADC), squamous cell carcinoma (SCC), adenosquamous carcinoma, hepatocellular carcinoma, and renal cell carcinoma (RCC), which are known cancers with a statistically significantly low incidence of alternative lengthening of telomeres. Cases were divided into 2 groups as follows: longer and shorter telomeres, according to the median TL of cancer cells and CAFs. The statistical significance of TL in cancer cells and CAFs on clinicopathological characteristics and prognosis was analyzed. Results There was a close association between TL in cancer cells and CAFs. Longer telomeres in cancer cells and CAFs were associated with aggressive features such as advanced stage, high mitosis score and nuclear score, poorly differentiated cancer, and desmoplastic stroma in ADC. Furthermore, a longer TL was an independent prognostic factor for ADC, SCC, and RCC. Conclusions Longer telomeres are associated with worse prognosis in ADC, SCC, and RCC. Thus, TL is a novel biomarker for the diagnosis of aggressive cancers with poor prognoses.
Recent Advances in “Functional Engineering of Articular Cartilage Zones by Polymeric Biomaterials Mediated with Physical, Mechanical, and Biological/Chemical Cues”
Authors: Dorsa Dehghan‐Baniani, Babak Mehrjou, Paul K. Chu, Wayne Yuk Wai Lee, Hongkai Wu
Journal: Advanced Healthcare Materials (2022)

Abstract Articular cartilage (AC) plays an unquestionable role in joint movements but unfortunately the healing capacity is restricted due to its avascular and acellular nature. While cartilage tissue engineering has been lifesaving, it is very challenging to remodel the complex cartilage composition and architecture with gradient physio–mechanical properties vital to proper tissue functions. To address these issues, a better understanding of the intrinsic AC properties and how cells respond to stimuli from the external microenvironment must be better understood. This is essential in order to take one step closer to producing functional cartilaginous constructs for clinical use. Recently, biopolymers have aroused much attention due to their versatility, processability, and flexibility because the properties can be tailored to match the requirements of AC. This review highlights polymeric scaffolds developed in the past decade for reconstruction of zonal AC layers including the superficial zone, middle zone, and deep zone by means of exogenous stimuli such as physical, mechanical, and biological/chemical signals. The mimicked properties are reviewed in terms of the biochemical composition and organization, cell fate (morphology, orientation, and differentiation), as well as mechanical properties and finally, the challenges and potential ways to tackle them are discussed.